MCPIP1 RNase is aberrantly distributed in psoriatic epidermis and rapidly induced by IL-17A.
MCPIP1 RNase is aberrantly distributed in psoriatic epidermis and rapidly induced by IL-17A.
Citació
- Ruiz-Romeu E, Ferran M, Giménez-Arnau A, Bugara B, Lipert B, Jura J. et al. MCPIP1 RNase is aberrantly distributed in psoriatic epidermis and rapidly induced by IL-17A. J Invest Dermatol. 2016 Aug;136(8):1599-607. doi: 10.1016/j.jid.2016.04.030
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Resum
ZC3H12A, which encodes the RNase monocyte chemotactic protein-induced protein 1 (MCPIP1), is up-regulated in psoriatic skin and reduced to normal levels after clinical treatments with anti-IL-17A/IL-17R neutralizing antibodies. In IL-17A-stimulated keratinocytes, MCPIP1 is rapidly increased at the transcript and protein levels. Also, IL-17A was found to be the main inducer of ZC3H12A expression in keratinocytes treated with supernatants derived from a Streptococcus pyogenes-activated psoriatic ex vivo model based on the co-culture of psoriatic cutaneous lymphocyte-associated antigen (CLA(+)) T cells and lesional epidermal cells. Moreover, MCPIP1 was aberrantly distributed in the suprabasal layers of psoriatic epidermis. In psoriatic samples, IL-17A-stimulated epidermal cell suspensions showed an increased MCPIP1 expression, especially in the mid-differentiated cellular compartment. The knockdown of ZC3H12A showed that this RNase participates in the regulation of the mRNAs present in suprabasal differentiated keratinocytes. Furthermore, JAK/STAT3 inhibition prevented the IL-17A-dependent induction of MCPIP1. In the mouse model of imiquimod-induced psoriasis, Zc3h12a expression was abrogated in Il17ra(-/-) mice. These results support the notion that IL-17A-mediated induction of MCPIP1 is involved in the regulation of local altered gene expression in suprabasal epidermal layers in psoriasis.Col·leccions
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